The long-term objective of this program is to understand the mechanisms of cellular changes fundamental to neoplastic transformation. Mammalian cells in culture represent a model with which to study changes in normal growth regulation. Tumor cells have been shown to produce growth factors with mitogenic activity, and gene products of certain tumor viruses are virtually identical to normal cellular homologues which participate in regulation of cell proliferation. Since mammalian cells in culture usually require undefined serum as a mitogenic stimulant, rigorous assessment of the biologic impact of retroviral gene products on growth control first required development of serum-free culture systems. Present studies in serum-free medium with insulin show sis gene complements requirements for sustained proliferation. Analysis of other genes linked to transduction of extracellular mitotic stimuli or intracellular sensing mechanisms for DNA, RNA or protein synthesis is in progress.